Patatin-Like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C

Luca Valenti, Mariagrazia Rumi, Enrico Galmozzi, Alessio Aghemo, Benedetta Del Menico, Stella De Nicola, Paola Dongiovanni, Marco Maggioni, Anna Ludovica Fracanzani, Raffaela Rametta, Massimo Colombo, Silvia Fargion

Research output: Contribution to journalArticle

Abstract

Steatosis has been reported to negatively influence the natural history of chronic hepatitis C (CHC), but controversy remains over its causal role due to the confounding effect of adiposity, insulin resistance, and diabetes. The rs738409 C>G patatin-like phospholipase domain-containing 3 (PNPLA3) single nucleotide polymorphism (SNP), encoding for the I148M protein variant, influences liver fat without affecting insulin resistance and body composition. The aim of this study was to evaluate the effect of the rs738409 CG genotype on liver fat and fibrosis in CHC patients. We also explored the possible effect of PNPLA3 genotype on other steatosis-related complications, namely, treatment failure and hepatocellular carcinoma (HCC) development. To this end we considered two independent series of 325 and 494 CHC patients with available DNA and liver biopsy followed at tertiary referral centers in northern Italy. The rs738409 genotype was determined by a Taqman assay. The rs738409 GG genotype, observed in 10% of patients, was associated with steatosis independently of age, sex, body mass index (BMI), diabetes, alcohol intake, and viral genotype (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.4-2.7; P <0.001). The association with rs738409 genotype was confirmed for severe steatosis, was independent of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) values, and was observed in all viral genotypes but the 3. The rs738409 GG genotype was associated with fibrosis stage and cirrhosis (OR 1.47, 95% CI 1.2-1.9; P = 0.002), treatment response (n = 470; OR 0.63, 95% CI 0.4-0.8; P = 0.006), and HCC occurrence (n = 325; OR 2.16, 95% CI 1.3-3.6; P = 0.002), independently of confounders. Conclusion: The rs738409 PNPLA3 genotype influences steatosis development in CHC and is independently associated with cirrhosis and other steatosis-related clinical outcomes, such as lack of response to antiviral treatment and possibly HCC.

Original languageEnglish
Pages (from-to)791-799
Number of pages9
JournalHepatology
Volume53
Issue number3
DOIs
Publication statusPublished - Mar 2011

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Phospholipases
Chronic Hepatitis C
Fatty Liver
Genotype
Odds Ratio
Confidence Intervals
Hepatocellular Carcinoma
Fibrosis
Insulin Resistance
Fats
Liver
Adiposity
Transferases
Body Composition
Treatment Failure
Alanine Transaminase
Tertiary Care Centers
Liver Cirrhosis
Italy
Antiviral Agents

ASJC Scopus subject areas

  • Hepatology

Cite this

@article{42110690c6e94c2eabd3b71a52258474,
title = "Patatin-Like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C",
abstract = "Steatosis has been reported to negatively influence the natural history of chronic hepatitis C (CHC), but controversy remains over its causal role due to the confounding effect of adiposity, insulin resistance, and diabetes. The rs738409 C>G patatin-like phospholipase domain-containing 3 (PNPLA3) single nucleotide polymorphism (SNP), encoding for the I148M protein variant, influences liver fat without affecting insulin resistance and body composition. The aim of this study was to evaluate the effect of the rs738409 CG genotype on liver fat and fibrosis in CHC patients. We also explored the possible effect of PNPLA3 genotype on other steatosis-related complications, namely, treatment failure and hepatocellular carcinoma (HCC) development. To this end we considered two independent series of 325 and 494 CHC patients with available DNA and liver biopsy followed at tertiary referral centers in northern Italy. The rs738409 genotype was determined by a Taqman assay. The rs738409 GG genotype, observed in 10{\%} of patients, was associated with steatosis independently of age, sex, body mass index (BMI), diabetes, alcohol intake, and viral genotype (odds ratio [OR] 1.90, 95{\%} confidence interval [CI] 1.4-2.7; P <0.001). The association with rs738409 genotype was confirmed for severe steatosis, was independent of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) values, and was observed in all viral genotypes but the 3. The rs738409 GG genotype was associated with fibrosis stage and cirrhosis (OR 1.47, 95{\%} CI 1.2-1.9; P = 0.002), treatment response (n = 470; OR 0.63, 95{\%} CI 0.4-0.8; P = 0.006), and HCC occurrence (n = 325; OR 2.16, 95{\%} CI 1.3-3.6; P = 0.002), independently of confounders. Conclusion: The rs738409 PNPLA3 genotype influences steatosis development in CHC and is independently associated with cirrhosis and other steatosis-related clinical outcomes, such as lack of response to antiviral treatment and possibly HCC.",
author = "Luca Valenti and Mariagrazia Rumi and Enrico Galmozzi and Alessio Aghemo and {Del Menico}, Benedetta and {De Nicola}, Stella and Paola Dongiovanni and Marco Maggioni and Fracanzani, {Anna Ludovica} and Raffaela Rametta and Massimo Colombo and Silvia Fargion",
year = "2011",
month = "3",
doi = "10.1002/hep.24123",
language = "English",
volume = "53",
pages = "791--799",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - Patatin-Like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C

AU - Valenti, Luca

AU - Rumi, Mariagrazia

AU - Galmozzi, Enrico

AU - Aghemo, Alessio

AU - Del Menico, Benedetta

AU - De Nicola, Stella

AU - Dongiovanni, Paola

AU - Maggioni, Marco

AU - Fracanzani, Anna Ludovica

AU - Rametta, Raffaela

AU - Colombo, Massimo

AU - Fargion, Silvia

PY - 2011/3

Y1 - 2011/3

N2 - Steatosis has been reported to negatively influence the natural history of chronic hepatitis C (CHC), but controversy remains over its causal role due to the confounding effect of adiposity, insulin resistance, and diabetes. The rs738409 C>G patatin-like phospholipase domain-containing 3 (PNPLA3) single nucleotide polymorphism (SNP), encoding for the I148M protein variant, influences liver fat without affecting insulin resistance and body composition. The aim of this study was to evaluate the effect of the rs738409 CG genotype on liver fat and fibrosis in CHC patients. We also explored the possible effect of PNPLA3 genotype on other steatosis-related complications, namely, treatment failure and hepatocellular carcinoma (HCC) development. To this end we considered two independent series of 325 and 494 CHC patients with available DNA and liver biopsy followed at tertiary referral centers in northern Italy. The rs738409 genotype was determined by a Taqman assay. The rs738409 GG genotype, observed in 10% of patients, was associated with steatosis independently of age, sex, body mass index (BMI), diabetes, alcohol intake, and viral genotype (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.4-2.7; P <0.001). The association with rs738409 genotype was confirmed for severe steatosis, was independent of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) values, and was observed in all viral genotypes but the 3. The rs738409 GG genotype was associated with fibrosis stage and cirrhosis (OR 1.47, 95% CI 1.2-1.9; P = 0.002), treatment response (n = 470; OR 0.63, 95% CI 0.4-0.8; P = 0.006), and HCC occurrence (n = 325; OR 2.16, 95% CI 1.3-3.6; P = 0.002), independently of confounders. Conclusion: The rs738409 PNPLA3 genotype influences steatosis development in CHC and is independently associated with cirrhosis and other steatosis-related clinical outcomes, such as lack of response to antiviral treatment and possibly HCC.

AB - Steatosis has been reported to negatively influence the natural history of chronic hepatitis C (CHC), but controversy remains over its causal role due to the confounding effect of adiposity, insulin resistance, and diabetes. The rs738409 C>G patatin-like phospholipase domain-containing 3 (PNPLA3) single nucleotide polymorphism (SNP), encoding for the I148M protein variant, influences liver fat without affecting insulin resistance and body composition. The aim of this study was to evaluate the effect of the rs738409 CG genotype on liver fat and fibrosis in CHC patients. We also explored the possible effect of PNPLA3 genotype on other steatosis-related complications, namely, treatment failure and hepatocellular carcinoma (HCC) development. To this end we considered two independent series of 325 and 494 CHC patients with available DNA and liver biopsy followed at tertiary referral centers in northern Italy. The rs738409 genotype was determined by a Taqman assay. The rs738409 GG genotype, observed in 10% of patients, was associated with steatosis independently of age, sex, body mass index (BMI), diabetes, alcohol intake, and viral genotype (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.4-2.7; P <0.001). The association with rs738409 genotype was confirmed for severe steatosis, was independent of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) values, and was observed in all viral genotypes but the 3. The rs738409 GG genotype was associated with fibrosis stage and cirrhosis (OR 1.47, 95% CI 1.2-1.9; P = 0.002), treatment response (n = 470; OR 0.63, 95% CI 0.4-0.8; P = 0.006), and HCC occurrence (n = 325; OR 2.16, 95% CI 1.3-3.6; P = 0.002), independently of confounders. Conclusion: The rs738409 PNPLA3 genotype influences steatosis development in CHC and is independently associated with cirrhosis and other steatosis-related clinical outcomes, such as lack of response to antiviral treatment and possibly HCC.

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U2 - 10.1002/hep.24123

DO - 10.1002/hep.24123

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